Primary Effusion Lymphoma, Multicentric Castleman's Disease, and Kaposi's Sarcoma in an HHV-8 and HIV-Positive Patient: A Case Report.

Primary effusion lymphoma (PEL), Kaposi's sarcoma (KS), and multicentric Castleman's disease (MCD) is an uncommon group of diseases included in the same spectrum with related characteristics. The coexistence of all of them in the same individual is a rare occurrence. We present the case of a 25-year-old patient diagnosed with human immunodeficiency virus (HIV) and the development of all these related pathologies. Despite the use of intensive treatment according to the latest recommendations, the evolution was unfavorable. This case reflects the need for new therapies and research in this field.

Primary Effusion Lymphoma-like Lymphoma Mimicking Tuberculous Pleural Effusion: Three Case Reports and a Literature Review.

Primary effusion lymphoma-like lymphoma (PEL-LL) is a rare lymphoma, localized in the body cavity without detectable tumor masses. Tuberculous pleural effusion is a form of extra pulmonary tuberculous. We herein report three cases of PEL-LL in patients with a history of pulmonary tuberculosis. Despite the presentation with lymphocyte predominance and high levels of adenosine deaminase, a notable characteristic of tuberculous pleural effusion, the patients were ultimately diagnosed with PEL-LL. Pleural fluid laboratory tests yield similar results for PEL-LL and tuberculous pleural effusion; therefore, cytological and immunophenotyping examinations are useful for their differential diagnosis and the determination of treatment.

Synchronous visceral Kaposi sarcoma and extracavitary primary effusion lymphoma in a patient with AIDS.

While infection should always lead the differential when a patient with AIDS presents with fever, inflammatory and malignant aetiologies should also be considered. With profound immunocompromise, malignancies can develop as sequelae of viral oncogene expression. Human herpesvirus 8 (HHV-8) infection drives several AIDS-related cancers including Kaposi sarcoma (KS), multicentric Castleman disease and primary effusion lymphoma (PEL), which can present simultaneously with variable clinical features. Herein, we describe a case of synchronous visceral KS and extracavitary PEL in a patient with AIDS. The patient was treated with systemic chemotherapy and remains in remission after four cycles. We review other cases of copresenting HHV-8-related malignancies, explore the salient pathomechanisms and clinical features of these cancers and discuss treatment strategies.

Extracavitary primary effusion lymphoma recurring with syphilis in an HIV-infected patient.

A 59-year-old Caucasian man infected with HIV, in remission from human herpes virus-8-positive extracavitary primary effusion lymphoma (EC-PEL), presented to a sexual health clinic with fever and rectal pain 10 weeks after a single episode of receptive anal sexual intercourse with another man. He was initially treated for a presumptive diagnosis of lymphogranuloma venereum proctitis, then for syphilis on positive serology. Rectosigmoidoscopy revealed a single ulcerated rectal mass; endoscopic biopsies confirmed the recurrence of EC-PEL. The patient received chemotherapy and went into remission. This is the first reported case of EC-PEL occurring synchronously with early syphilis, and specifically at the site of inoculation, which can be a major diagnostic challenge since both conditions may present with lymphadenopathy, mucosal involvement and constitutional symptoms. We reviewed the literature for similar cases and hypothesised that syphilis may have triggered the recurrence of this rare lymphoma.

Primary effusion lymphoma metachronous to multicentric Castleman disease in an immunocompetent patient.

Human Herpesvirus 8 (HHV8) has been associated with a wide spectrum of B-cell lymphoproliferative disorders, including Primary Effusion Lymphoma, Multicentric Castleman Disease, HHV8-positive Diffuse Large B-cell Lymphoma, not otherwise specified and germinotropic lymphoproliferative disorder. The association of different HHV8-related lymphoproliferative disorders is described in immunodeficient patients. We report a case of Primary Effusion Lymphoma metachronous to Multicentric Castleman Disease in an immunocompetent patient.

Kaposi Sarcoma in Association With an Extracavitary Primary Effusion Lymphoma Showing Unusual Intravascular Involvement: Report of a Case Harboring a FAM175A Germline Mutation.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma characterized by a malignant serous effusion involving body cavities. It usually associated with human herpes virus-8 (HHV-8) and coexpression of Epstein-Barr virus and mostly affects patients with HIV. We report a rare case of cutaneous PEL with an unusual intravascular presentation, combined with Kaposi sarcoma involving the skin, lung, and gastrointestinal tract. The molecular genetic analysis of the sarcoma and lymphoma components, using next-generation sequencing was performed. The patient was a 67-year-old man who presented with multiple cutaneous tumors and mass in the left lung. He died 17 hours after the admission to the hospital. At autopsy, in addition to the cutaneous lesions, tumors in the left lung and gastrointestinal mucosa were detected, and no effusions in the body cavities were seen. The biopsy from the cutaneous lesions, pulmonary, and intestinal tumors revealed histological and immunohistochemical features of Kaposi sarcoma. In addition, the skin biopsy specimens contained a diffuse infiltrate composed of large pleomorphic cells, with focal intravascular growth that were negative for pan B-cell markers, weakly positive for CD38 and CD138 but expressed CD3, HHV-8, and Epstein-Barr virus. Molecular genetic studies in this specimen revealed monoclonal rearrangements of the IgH gene. The diagnosis of PEL, solid variant, was made. Next-generation sequencing analysis of the tumorous and normal tissue detected a pathogenic germline mutation of the FAM175A gene and somatic mutations in BRCA2 and RAD51B (in both sarcoma and lymphoma specimens), and INPP4B and RICTOR (in lymphoma specimen only).

Panniculitis-Like Presentation of Extracavitary Primary Effusion Lymphoma.

Primary effusion lymphoma (PEL) is defined as a HHV-8-associated large B-cell lymphoma, which favors HIV-infected young adults, typically presenting as a serous (pleural, pericardial, or peritoneal) effusion with no identifiable tumor mass. Uncommon instances of lymphoid proliferations with the same morphology, immunophenotype, and molecular features as PEL, but occurring as a solid tumor mass without serous cavities involvement, have been termed extracavitary (or solid) variant of PEL. We hereby report the exceptional case of a HIV-associated extracavitary PEL primarily localized to the skin and exhibiting a panniculitis-like presentation. Primary cutaneous presentation of extracavitary PEL is exceedingly uncommon, with only 6 cases previously described in the literature. In light of its atypical immunophenotype, the differential diagnosis in case of skin involvement by extracavitary PEL is challenging: demonstration of HHV-8 infection in neoplastic cells is of pivotal importance. Our case is further atypical in that the lymphoid proliferation underwent complete and protracted regression solely by establishment of highly active antiretroviral therapy.

[Human herpes virus 8-negative primary effusion lymphoma-like lymphoma recurring as a tumor adjacent to the left atrium].

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma, usually presenting as serous effusions without detectable tumor masses, and it is universally associated with the human herpesvirus 8 (HHV8). In contrast, cases of HHV8-negative effusion lymphoma have been reported and termed as HHV8-negative PEL-like lymphoma. Here, we have reported a rare case of HHV8-negative PEL-like lymphoma that developed in the left atrium tumor 4 years after the pericardial drainage. A 74-year-old female was admitted due to cardiac tamponade caused by massive pericardial effusion. Pericardial drainage was performed, and cytopathologic examination of the fluid revealed atypical lymphoid cells consistent with an effusion lymphoma of B-cell lineage. The pericardial effusion was completely drained, and complete remission was achieved. After 4 years of the drainage, she developed syncope caused by arrhythmia. A computed tomography scan revealed a large tumor in the left atrium and multiple swollen mediastinal lymph nodes. Biopsy of one of the lymph nodes was performed, and its histology was consistent with diffuse large B-cell lymphoma. She was treated with chemotherapy, including rituximab, and complete remission was achieved again. Thus, our experience suggests that careful follow-up may be required in patients with HHV8-negative PEL-like lymphoma after complete remission has been achieved by the drainage.

Viral, immunologic, and clinical features of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is an aggressive HIV-associated lymphoma with a relatively poor prognosis in the era of effective HIV therapy. Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent, and ∼80% of tumors are coinfected with Epstein-Barr virus (EBV). A better understanding of how KSHV-related immune dysregulation contributes to the natural history of PEL will improve outcomes. Twenty patients with PEL diagnosed between 2000 and 2013, including 19 treated with modified infusional etoposide, vincristine, and doxorubicin with cyclophosphamide and prednisone (EPOCH), were identified. We compared their clinical, virologic, and immunologic features vs 20 patients with HIV-associated diffuse large B-cell lymphoma and 19 patients with symptomatic interleukin (IL)-6 related KSHV-associated multicentric Castleman disease. Survival analyses of treated patients with PEL were then performed to identify prognostic factors and cancer-specific mortality. Compared with HIV-associated diffuse large B-cell lymphoma, PEL was associated with significant hypoalbuminemia (P < .0027), thrombocytopenia (P = .0045), and elevated IL-10 levels (P < .0001). There were no significant differences in these parameters between PEL and KSHV-associated multicentric Castleman disease. Median overall survival in treated patients with PEL was 22 months, with a plateau in survival noted after 2 years. Three-year cancer-specific survival was 47%. EBV-positive tumor status was associated with improved survival (hazard ratio, 0.27; P = .038), and elevated IL-6 level was associated with inferior survival (hazard ratio, 6.1; P = .024). Our analysis shows that IL-6 and IL-10 levels contribute to the natural history of PEL. Inflammatory cytokines and tumor EBV status are the strongest prognostic factors. Pathogenesis-directed first-line regimens are needed to improve overall survival in PEL.

A 32-Year-Old Man With HIV Infection, Pleural Effusions, and Lymphadenopathy.

CASE PRESENTATION: A 32-year-old man presented with fever, nonproductive cough, diffuse lymphadenopathy, and polyarticular pain for 2 weeks. His medical history included HIV diagnosed 10 years ago, anal intraepithelial neoplasia, Kaposi sarcoma, and herpes simplex virus-2 infection. The patient was not receiving antiretroviral therapy or antibiotic prophylaxis, and his last known CD4 count a month before was 45 cells/mm3. He was prescribed a course of doxycycline by his primary care physician, which did not improve his symptoms.

Multiple remissions of extracavitary primary effusion lymphoma treated with a single cycle of liposomal doxorubicin in a patient infected with HIV.

Primary effusion lymphoma (pel) is a rare human herpesvirus 8 (hhv8)-related large B cell lymphoma with plasmablastic, immunoblastic, or anaplastic features that often carries a poor prognosis. This lymphoma occurs mainly in patients with hiv infection, most often with Epstein-Barr virus (ebv) co-infection, and usually presents as body cavity effusions or, less commonly, as extracavitary lesions without effusion (ec-pel). Chemotherapeutic treatment options are limited and require concurrent antiretroviral therapy (art). Here, we report the case of an adult patient with hiv infection and chronic hepatitis E virus (hev) co-infection who had low CD4 T cell recovery after years of art. The patient then developed a cutaneous ec-pel which rapidly regressed after 1 cycle of liposomal doxorubicin (ld) for his Kaposi sarcoma (ks) before treatment with chop chemotherapy. He had previously received numerous cycles of ld for cutaneous ks over 2 years. Because of the patient's low CD4 T cell count, hev co-infection, and earlier unexpected remission of ec-pel before chop, the patient opted for a single trial of ld before other options. Surprisingly, he experienced a complete remission lasting 18 months. Subsequently, his ec-pel relapsed twice at 31 and at 41 months after the initial diagnosis. Upon recurrence, a similar single cycle of ld was given, which again induced remission. The patient today is in complete remission after a total of 4 ld infusions over 54 months. This patient represents a unique case of hiv-with-hhv8-related, ebv-negative ec-pel with chronic hev coinfection, in which rapid remission was achieved after a single cycle of ld, suggesting an antiviral response in addition to the chemotherapeutic effect.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma presenting with cardiac tamponade: A case report.

RATIONALE: Primary effusion lymphoma (PEL) is a rare disease of lymphomatous effusion in the body cavities in the absence of detectable mass and lymphadenopathy. PEL is predominantly related to the immunosuppressed patients infected with human herpes virus 8 (HHV-8). PEL-like lymphoma is negative for HHV-8 and human immunodeficiency virus (HIV) unlike PEL. The pathogenesis and prognosis of PEL-like lymphoma are unclear and there is no established treatment yet. PATIENT CONCERNS: A 73-year-old male patient was admitted for evaluation of dyspnea on exertion with 1-week duration. His relevant examinations were completed. DIAGNOSES: PEL-like lymphoma was diagnosed. INTERVENTIONS: The patient received chemotherapy including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), and palliative whole-brain radiotherapy, sequentially. OUTCOMES: He died 3 months after the diagnosis. LESSON: Although the prognosis of PEL-like lymphoma may be better than PEL, our case showed poor disease course despite chemotherapy.

KSHV-associated extracavitary primary effusion lymphoma in an HIV seronegative patient: a case report and review of the literature.

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin's lymphoma presenting as a lymphomatous effusion and absence of a solid tumor mass. Extracavitary PEL (EC-PEL) is a subtype of PEL with the absence of an effusion but presence of solid tumor. PEL and EC-PEL share the same histopathologic and immunophenotypic features. Kaposi sarcoma-associated herpesvirus (KSHV) positivity is seen universally in these malignancies and is a requisite for diagnosis. Most cases are seen to occur in HIV positive individuals. We present a unique case of a 21-year-old male who presented with ongoing chest pain and right hip pain found to have an extensive lytic lesion of the right iliac bone, a paratracheal mass and a large pelvic mass. All the involved sites were FDG (F-18 fluorodeoxyglucose)-avid on PET-CT scan. The patient was seronegative for HIV with no risk factors for immunosuppression. A biopsy of the pelvic mass and bone marrow showed large atypical cells with irregular multi-lobulated nuclei, prominent nucleoli, and abundant amphophilic cytoplasm. The cells were positive for MUM1, in situ hybridization for EBV-encoded RNA (EBER), and KSHV, while negative for B-cell and T-cell markers. The patient was treated with six cycles of DA-EPOCH with a follow up PET scan showing a decrease in size of the masses and bone lesion and conversion to non-FDG-avid status. To the best of our knowledge, our case is the first in published English literature with bone involvement with EC-PEL regardless of HIV status. We review the reported cases of EC-PEL including their presentation, diagnostic features, treatment and outcomes.

Primary effusion lymphoma involving cerebrospinal fluid, deep cervical lymph nodes and adenoids. Report of a case supporting the lymphatic connection between brain and lymph nodes.

We describe an unusual presentation of primary effusion lymphoma in CSF of a 45-year-old HIV-positive man, with no evidence of involvement of pleural, peritoneal or pericardial cavities. Cytologic examination and flow cytometric analysis suggested the diagnosis, eventually made in an excised deep cervical lymph node, in which the neoplastic cells involved selectively the sinuses. This case represents the fifth reported example of CSF involvement by this type of lymphoma, and supports the alleged connection between CSF and cervical lymph nodes via lymphatic vessels. Interestingly, review of an adenoidectomy specimen obtained 9 months before presentation for nonspecific complaints showed rare clusters of neoplastic cells involving surface epithelium and chorium, a finding that might represent a homing mechanism and implies an asymptomatic, occult phase of lymphoma development.